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dc.contributor.authorGłodzik, Den
dc.contributor.authorPurdie, Cen
dc.contributor.authorRye, IHen
dc.contributor.authorSimpson, PTen
dc.contributor.authorStaaf, Jen
dc.contributor.authorSpan, PNen
dc.contributor.authorRussnes, HGen
dc.contributor.authorNik-Zainal Abidin, Serenaen
dc.date.accessioned2018-11-17T00:31:10Z
dc.date.available2018-11-17T00:31:10Z
dc.date.issued2018-11en
dc.identifier.issn0923-7534
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285358
dc.description.abstractBackground Complex clusters of rearrangements in cancer genomes are a challenge to interpret. Some are clear amplifications of driver oncogenes but others are less well understood. Detailed analysis of rearrangements within these complex clusters could reveal new insights into selection, and underlying mutational mechanisms. Results Here, we systematically investigate rearrangements that are densely clustered in individual tumours in a cohort of 560 breast cancers. Applying an agnostic approach, we identify 21 hotspots where clustered rearrangements recur across cancers. Some hotspots coincide with known oncogene loci including CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC. Others contain cancer genes not typically associated with breast cancer: MCL1, PTP4A1 and MYB. Intriguingly, we identify clustered rearrangements that physically connect distant hotspots. In particular, we observe simultaneous amplification of chr8:ZNF703/FGFR1 and chr11:CCND1 where deep analysis reveals that a chr8-chr11 translocation is likely to be an early, critical, initiating event. Conclusions We present an overview of complex rearrangements in breast cancer, highlighting a potential new way for detecting drivers and revealing novel mechanistic insights into the formation of two common amplicons.
dc.format.mediumPrinten
dc.languageengen
dc.publisherOUP
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBreasten
dc.subjectChromosomes, Human, Pair 8en
dc.subjectChromosomes, Human, Pair 11en
dc.subjectHumansen
dc.subjectBreast Neoplasmsen
dc.subjectTranslocation, Geneticen
dc.subjectCyclin D1en
dc.subjectCarrier Proteinsen
dc.subjectGenomicsen
dc.subjectAge Distributionen
dc.subjectGene Amplificationen
dc.subjectOncogenesen
dc.subjectAlgorithmsen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectReceptor, Fibroblast Growth Factor, Type 1en
dc.subjectGenetic Locien
dc.subjectDatasets as Topicen
dc.subjectWhole Genome Sequencingen
dc.titleMutational mechanisms of amplifications revealed by analysis of clustered rearrangements in breast cancers.en
dc.typeArticle
prism.endingPage2231
prism.issueIdentifier11en
prism.publicationDate2018en
prism.publicationNameAnnals of oncology : official journal of the European Society for Medical Oncologyen
prism.startingPage2223
prism.volume29en
dc.identifier.doi10.17863/CAM.32725
dcterms.dateAccepted2018-09-07en
rioxxterms.versionofrecord10.1093/annonc/mdy404en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-11en
dc.contributor.orcidGłodzik, D [0000-0001-8112-9073]
dc.contributor.orcidSimpson, PT [0000-0002-4816-8289]
dc.contributor.orcidSpan, PN [0000-0002-1930-6638]
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.identifier.eissn1569-8041
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (23916)
pubs.funder-project-idCancer Research UK (25274)
pubs.funder-project-idEC FP7 CP (242006)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International